TY - JOUR
T1 - Regulation of Plasmodium sporozoite motility by formulation components
AU - de Korne, Clarize M
AU - Lageschaar, Luuk T
AU - van Oosterom, Matthias N
AU - Baalbergen, Els
AU - Winkel, Beatrice M F
AU - Chevalley-Maurel, Severine C
AU - Velders, Aldrik H
AU - Franke-Fayard, Blandine M D
AU - van Leeuwen, Fijs W B
AU - Roestenberg, Meta
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/5/2
Y1 - 2019/5/2
N2 - BACKGROUND: The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on the parasite's potential to migrate in the human host. Key components of the parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however the regulation of this machinery is an unknown process.METHODS: In vitro microscopic live imaging of parasites in different formulations was performed and analysed, with the quantitative analysis software SMOOTIn vitro, their motility; their adherence capacity, movement pattern and velocity during forward locomotion.RESULTS: SMOOTIn vitro enabled the detailed analysis of the regulation of the motility machinery of Plasmodium berghei in response to specific (macro)molecules in the formulation. Albumin acted as an essential supplement to induce parasite attachment and movement. Glucose, salts and other whole serum components further increased the attachment rate and regulated the velocity of the movement.CONCLUSIONS: Based on the findings can be concluded that a complex interplay of albumin, glucose and certain salts and amino acids regulates parasite motility. Insights in parasite motility regulation by supplements in solution potentially provide a way to optimize the whole-parasite malaria vaccine formulation.
AB - BACKGROUND: The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on the parasite's potential to migrate in the human host. Key components of the parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however the regulation of this machinery is an unknown process.METHODS: In vitro microscopic live imaging of parasites in different formulations was performed and analysed, with the quantitative analysis software SMOOTIn vitro, their motility; their adherence capacity, movement pattern and velocity during forward locomotion.RESULTS: SMOOTIn vitro enabled the detailed analysis of the regulation of the motility machinery of Plasmodium berghei in response to specific (macro)molecules in the formulation. Albumin acted as an essential supplement to induce parasite attachment and movement. Glucose, salts and other whole serum components further increased the attachment rate and regulated the velocity of the movement.CONCLUSIONS: Based on the findings can be concluded that a complex interplay of albumin, glucose and certain salts and amino acids regulates parasite motility. Insights in parasite motility regulation by supplements in solution potentially provide a way to optimize the whole-parasite malaria vaccine formulation.
KW - Albumins/pharmacology
KW - Animals
KW - Culicidae/parasitology
KW - Culture Media/chemistry
KW - Female
KW - Glucose/pharmacology
KW - Intravital Microscopy
KW - Locomotion/drug effects
KW - Malaria/parasitology
KW - Mice
KW - Plasmodium berghei/drug effects
KW - Software
KW - Sporozoites/physiology
U2 - 10.1186/s12936-019-2794-y
DO - 10.1186/s12936-019-2794-y
M3 - Article
C2 - 31046772
SN - 1475-2875
VL - 18
JO - Malaria Journal
JF - Malaria Journal
IS - 1
M1 - 155
ER -